COVID-19 and diabetes mellitus: from pathophysiology to clinical management

Abstract

Initial studies found increased severity of coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in patients with diabetes mellitus. Furthermore, COVID-19 might also predispose infected individuals to hyperglycaemia. Interacting with other risk factors, hyperglycaemia might modulate immune and inflammatory responses, thus predisposing patients to severe COVID-19 and possible lethal outcomes. Angiotensin-converting enzyme 2 (ACE2), which is part of the renin–angiotensin–aldosterone system (RAAS), is the main entry receptor for SARS-CoV-2; although dipeptidyl peptidase 4 (DPP4) might also act as a binding target. Preliminary data, however, do not suggest a notable effect of glucose-lowering DPP4 inhibitors on SARS-CoV-2 susceptibility. Owing to their pharmacological characteristics, sodium–glucose cotransporter 2 (SGLT2) inhibitors might cause adverse effects in patients with COVID-19 and so cannot be recommended. Currently, insulin should be the main approach to the control of acute glycaemia. Most available evidence does not distinguish between the major types of diabetes mellitus and is related to type 2 diabetes mellitus owing to its high prevalence. However, some limited evidence is now available on type 1 diabetes mellitus and COVID-19. Most of these conclusions are preliminary, and further investigation of the optimal management in patients with diabetes mellitus is warranted.

Abstract

The pathophysiology of coronavirus disease 19 (COVID-19) and diabetes mellitus are interlinked, and diabetes mellitus is associated with severe COVID-19 outcomes. This Review highlights new advances in diabetes mellitus and COVID-19, considering disease mechanisms and clinical management of patients with diabetes mellitus in the ongoing pandemic.

Key points

• Underlying diabetes mellitus and cardiovascular diseases are considered risk factors for increased coronavirus disease 2019 (COVID-19) disease severity and worse outcomes, including higher mortality.

• Potential pathogenetic links between COVID-19 and diabetes mellitus include effects on glucose homeostasis, inflammation, altered immune status and activation of the renin–angiotensin–aldosterone system (RAAS).

• During the COVID-19 pandemic, tight control of glucose levels and prevention of diabetes complications might be crucial in patients with diabetes mellitus to keep susceptibility low and to prevent severe courses of COVID-19.

• Evidence suggests that insulin and dipeptidyl peptidase 4 inhibitors can be used safely in patients with diabetes mellitus and COVID-19; metformin and sodium–glucose cotransporter 2 inhibitors might need to be withdrawn in patients at high risk of severe disease.

• Pharmacological agents under investigation for the treatment of COVID-19 can affect glucose metabolism, particularly in patients with diabetes mellitus; therefore, frequent blood glucose monitoring and personalized adjustment of medications are required.

• As COVID-19 lacks definitive treatment so far, patients with diabetes mellitus should follow general preventive rules strictly and monitor glucose levels more frequently, engage in physical activity, eat healthily and control other risk factors.